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Serine threonine kinase 17A (STK17A) is a ubiquitously expressed kinase originally identified as a regulator of apoptosis; however, whether it functionally contributes to colorectal cancer has not been established. Here, we have analyzed STK17A in colorectal cancer and demonstrated decreased expression of STK17A in primary tumors, which is further reduced in metastatic lesions, indicating a potential role in regulating the metastatic cascade. Interestingly, changes in STK17A expression did not modify proliferation, apoptosis, or sensitivity of colorectal cancer cell lines to treatment with the chemotherapeutic 5-fluorouracil. Instead, STK17A knockdown induced a robust mesenchymal phenotype consistent with the epithelial–mesenchymal transition, including spindle-like cell morphology, decreased expression of adherens junction proteins, and increased migration and invasion. Additionally, overexpression of STK17A decreased cell size and induced widespread membrane blebbing, a phenotype often associated with activation of cell contractility. Indeed, STK17A-overexpressing cells displayed heightened phosphorylation of myosin light chain in a manner dependent on STK17A catalytic activity. Finally, patient-derived tumor organoid cultures were used to more accurately determine STK17A's effect in primary human tumor cells. Loss of STK17A induced morphologic changes, decreased E-cadherin, increased invasion, and augmented organoid attachment on 2D substrates, all together suggesting a more metastatic phenotype. Collectively, these data indicate a novel role for STK17A in the regulation of epithelial phenotypes and indicate its functional contribution to colorectal cancer invasion and metastasis.Implications:Loss of serine threonine kinase 17A occurs in colorectal cancer metastasis, induces mesenchymal morphologies, and contributes to tumor cell invasion and migration in colorectal cancer.

Supplemental Figure 1. STK17A expression does not correlate with CRC patient survival. Supplemental Figure 2. Attenuated morphological characteristics observed with decreased STK17A KD. Supplemental Figure 3. STK17A does not affect proliferation or viability of CRC cells. Supplemental Figure 4. STK17A expression KD human tumor organoid lines. Supplemental Figure 5. No phenotype induced by STK17A loss in HTO3.

Supplementary Figure 1. Specificity of GFI1 antibody. Supplementary Figure 2. Cell cycle and apoptosis analysis of GFI1-expressing CRC cancer cell lines in vitro. Supplementary Figure 3. Expression of CDX2 in the intestine. Supplementary Figure 4. Loss of Gfi1 affects secretory cell lineages.

Supplemental Table 1. qRT-PCR and mutagenesis primer sequences. Supplemental Table 2. Clinical features of human tumors from which organoid lines were derived. Supplemental Table 3. Components of complete human organoid media.

Supplementary Figure 2 from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

Myeloid Translocation Gene, Related-1 (MTGR1) CBFA2T2 is a member of the Myeloid Translocation Gene (MTG) family of transcriptional corepressors. The remaining two family members, MTG8 (RUNX1T1) and MTG16 (CBFA2T3) are identified as targets of chromosomal translocations in acute myeloid leukemia (AML). Mtgr1−/− mice have defects in intestinal lineage allocation and wound healing. Moreover, these mice show signs of impaired intestinal stem cell function. Based on these phenotypes, we hypothesized that MTGR1 may influence tumorigenesis arising in an inflammatory background. We report that Mtgr1−/− mice were protected from tumorigenesis when injected with azoxymethane (AOM) and then subjected to repeated cycles of dextran sodium sulfate (DSS). Tumor cell proliferation was comparable, but Mtgr1−/− tumors had significantly higher apoptosis rates. These phenotypes were dependent on epithelial injury, the resultant inflammation, or a combination of both as there was no difference in aberrant crypt foci (ACF) or tumor burden when animals were treated with AOM as the sole agent. Gene expression analysis indicated that Mtgr1−/− tumors had significant upregulation of inflammatory networks, and immunohistochemistry (IHC) for immune cell subsets revealed a marked multilineage increase in infiltrates, consisting predominately of CD3+ and natural killer T (NKT) cells as well as macrophages. Transplantation of wild type (WT) bone marrow into Mtgr1−/− mice, and the reciprocal transplant, did not alter the phenotype, ruling out an MTGR1 hematopoietic cell-autonomous mechanism. Our findings indicate that MTGR1 is required for efficient inflammatory carcinogenesis in this model, and implicate its dysfunction in colitis-associated carcinoma. This represents the first report functionally linking MTGR1 to intestinal tumorigenesis. Cancer Res; 71(4); 1302–12. ©2011 AACR.

The glutathione peroxidases, a family of selenocysteine-containing redox enzymes, play pivotal roles in balancing the signaling, immunomodulatory, and deleterious effects of reactive oxygen species (ROS). The glutathione peroxidase GPX3 is the only extracellular member of this family, suggesting it may defend cells against ROS in the extracellular environment. Notably, GPX3 hypermethylation and underexpression occur commonly in prostate, gastric, cervical, thyroid, and colon cancers. We took a reverse genetics approach to investigate whether GPX3 would augment inflammatory colonic tumorigenesis, a process characterized by oxidative stress and inflammation, comparing Gpx3−/− mice in an established two-stage model of inflammatory colon carcinogenesis. Gpx3-deficient mice exhibited an increased tumor number, though not size, along with a higher degree of dysplasia. In addition, they exhibited increased inflammation with redistribution toward protumorigenic M2 macrophage subsets, increased proliferation, hyperactive WNT signaling, and increased DNA damage. To determine the impact of acute gene loss in an established colon cancer line, we silenced GPX3 in human Caco2 cells, resulting in increased ROS production, DNA damage and apoptosis in response to oxidative stress, combined with decreased contact-independent growth. Taken together, our results suggested an immunomodulatory role for GPX3 that limits the development of colitis-associated carcinoma. Cancer Res; 73(3); 1245–55. ©2012 AACR.

PDF file - 2063K, Gpx3 is decreased in plasma of mice subjected to the AOM/DSS protocol. Western blot of Gpx3 protein expression in plasma from WT water treated and AOM/DSS treated mice (top). Quantification is presented as fold change intensity and the graph (bottom) displays plasma Gpx3 protein in the mice shown in the western blot above. P=0.046.

Supplementary Table 2 from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

Supplementary Figure 1 from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

Supplementary Figure 3 from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

PDF file - Gpx3 expression is highest in Caco2 cells. A) Gpx3 expression was analyzed within a cohort of colorectal cancer cell lines. The graph demonstrates fold-change of triplicate samples after analysis by the delta deltaCt method. B) Western blot for Gpx3 expression in Caco2 and HCT116 cells.

PDF file - 2275K, Gpx3 expression is downregulated in human colon cancer samples. A) GPX3 expression is significantly downregulated in adenomas and colorectal cancer patients compared with normal adjacent colon tissues. **P

PDF file - 2173K, Absence of Gpx3 does not modify weight change in response to AOM/DSS exposure. Percentage weight loss at day 0 and day 7 of each cycle throughout the course of the AOM/DSS protocol. P=n.s.

PDF file - 1974K, Gpx3 expression is not increased in tumor compared to normal tissue. Normal and tumor tissue mRNA expression of Gpx3 in WT normal adjacent and WT tumor tissue post-AOM/DSS. Error bars represent standard error of four mice performed in triplicate. P=n.s.

Supplementary Table 1 from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

Supplementary Legends for Figures and Tables from MTGR1 Is Required for Tumorigenesis in the Murine AOM/DSS Colitis-Associated Carcinoma Model

Deterioration of the end regions of prestressed concrete bridge girders is commonly observed in the field when girders are exposed to chloride-laden water that has leaked through failed expansion joints. Because the deterioration is often localized to the end regions of the girders, reliable repair techniques can provide a means to extend girder service life, avoiding the need for immediate superstructure replacement. To evaluate different repair methods and identify key design considerations for end region repair, shear tests to failure were conducted on prestressed concrete girders extracted from a decommissioned superstructure. Three repair systems were evaluated: an externally bonded fiber-reinforced-polymer (FRP) system, a near-surface-mounted FRP system, and a concrete end block. Only the externally bonded FRP system successfully restored both the strength and initial stiffness of the girder. Although the other two methods were not successful, the tests on the repaired girders highlight important factors that must be considered when designing repairs or conducting further research. The tests also demonstrate that end region deterioration can cause significant (> 40%) reductions in strength, underscoring the importance of addressing such deterioration observed in the field.

The gene mutated in colorectal cancer (MCC) encodes a coiled-coil protein implicated, as its name suggests, in the pathogenesis of hereditary human colon cancer. To date, however, the contributions of MCC to intestinal homeostasis and disease remain unclear. Here, we examine the subcellular localization of MCC, both at the mRNA and protein levels, in the adult intestinal epithelium. Our findings reveal that Mcc transcripts are restricted to proliferating crypt cells, including Lgr5+ stem cells, where the Mcc protein is distinctly associated with the centrosome. Upon intestinal cellular differentiation, Mcc is redeployed to the apical domain of polarized villus cells where non-centrosomal microtubule organizing centers (ncMTOCs) are positioned. Using intestinal organoids, we show that the shuttling of the Mcc protein depends on phosphorylation by casein kinases 1δ and ε, which are critical modulators of WNT signaling. Together, our findings support a role for MCC in establishing and maintaining the cellular architecture of the intestinal epithelium as a component of both the centrosome and ncMTOC.

Cancer cells characteristically consume glucose through Warburg metabolism1, a process that forms the basis of tumour imaging by positron emission tomography (PET). Tumour-infiltrating immune cells also rely on glucose, and impaired immune cell metabolism in the tumour microenvironment (TME) contributes to immune evasion by tumour cells2–4. However, whether the metabolism of immune cells is dysregulated in the TME by cell-intrinsic programs or by competition with cancer cells for limited nutrients remains unclear. Here we used PET tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the TME. Notably, myeloid cells had the greatest capacity to take up intratumoral glucose, followed by T cells and cancer cells, across a range of cancer models. By contrast, cancer cells showed the highest uptake of glutamine. This distinct nutrient partitioning was programmed in a cell-intrinsic manner through mTORC1 signalling and the expression of genes related to the metabolism of glucose and glutamine. Inhibiting glutamine uptake enhanced glucose uptake across tumour-resident cell types, showing that glutamine metabolism suppresses glucose uptake without glucose being a limiting factor in the TME. Thus, cell-intrinsic programs drive the preferential acquisition of glucose and glutamine by immune and cancer cells, respectively. Cell-selective partitioning of these nutrients could be exploited to develop therapies and imaging strategies to enhance or monitor the metabolic programs and activities of specific cell populations in the TME. Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.

Purpose MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. Methods HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. Results 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4–5 for all measures). In HVs, mean ART was 15.7 min (range 4–35), comparable to mean of 16.1 (range 7–33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. Conclusions Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

Infection of pulmonary endothelial cells by Pseudomonas aeruginosa induces the production and release of cytotoxic oligomeric tau and Aβ from the endothelial cells. Cystatin C, which is also secreted by the endothelial cells, can suppress the cytotoxic activity of Aβ. Whether cystatin C directly impacts oligomeric tau remains to be determined. Image produced with BioRender., Infection of rat pulmonary microvascular endothelial cells with the bacterium Pseudomonas aeruginosa induces the production and release of cytotoxic oligomeric tau and beta amyloid (Aβ). Here, we characterized these cytotoxic amyloids. Cytotoxic behavior and oligomeric tau were partially resistant to digestion with proteinase K, but cytotoxicity was abolished by various denaturants including phenol, diethylpyrocarbonate (DEPC), and 1,1,1,3,3,3‐hexafluoro‐2‐isopropanol (HFIP). Ultracentrifugation for 8 h at 150 000 g was required to remove cytotoxic activity from the supernatant. Ultracentrifugation, DEPC treatment, and immunodepletion using antibodies against Aβ also demonstrated that cytoprotective protein(s) are released from endothelial cells during P. aeruginosa infection. Mass spectrometry of endothelial cell culture media following P. aeruginosa infection allowed identification of multiple potential secreted modulators of Aβ, including cystatin C, gelsolin, and ApoJ/clusterin. Immunodepletion, co‐immunoprecipitation, and ultracentrifugation determined that the cytoprotective factor released during infection of endothelial cells by P. aeruginosa is cystatin C, which appears to be in a complex with Aβ. Cytoprotective cystatin C may provide a novel therapeutic avenue for protection against the long‐term consequences of infection with P. aeruginosa.

Within the state of Indiana, there are approximately 9,000 structures with unsupported span lengths that range from 4 ft to 20 ft that the Indiana Department of Transportation (INDOT) is responsible for maintaining. These structures are referred to as large culverts by INDOT. The agency recognized the need to improve culvert inspection procedures so that inspection data that is collected can provide essential information to asset engineers who make decisions regarding culvert management. The purpose of the project described in this report was to identify the best practices for inspection and management of these structures to develop guidelines to optimize the resources allocated for the maintenance and inspection of large culvert structures. The study found that standardizing the inspection process and evaluation criteria for inspection will positively impact the overall performance of the inventory of these structures. A proposed large culvert inspection manual accompanies this report and provides a detailed guide for large culvert inspection.

Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (iBD) and colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium-induced (DSS-induced) colitis. Transcriptomic analyses implicated increased Ephrussi box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a mouse model with a point mutation that attenuates MTG16:E protein interactions (Mtg16(P20ST)), we showed that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared with unaffected controls. Finally, uncoupling MTG16:E protein interactions partially phenocopied the enhanced tumorigenicity of Mtg16(-/)(-) colon in the azoxymethane/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets. is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.

Aberrant epithelial differentiation and regeneration contribute to colon pathologies including inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). MTG16 (CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency in mice exacerbates colitis and increases tumor burden in CAC, though the underlying mechanisms remain unclear. Here, we identified MTG16 as a central mediator of epithelial differentiation, promoting goblet and restraining enteroendocrine cell development in homeostasis and enabling regeneration following dextran sulfate sodium (DSS)-induced colitis. Transcriptomic analyses implicated increased E box-binding transcription factor (E protein) activity in MTG16-deficient colon crypts. Using a novel mouse model with a point mutation that disrupts MTG16:E protein complex formation (Mtg16P209T), we established that MTG16 exerts control over colonic epithelial differentiation and regeneration by repressing E protein-mediated transcription. Mimicking murine colitis, MTG16 expression was increased in biopsies from patients with active IBD compared to unaffected controls. Finally, uncoupling MTG16:E protein interactions only partially phenocopied the enhanced tumorigenicity of Mtg16-/- colon in the azoxymethane(AOM)/DSS-induced model of CAC, indicating that MTG16 protects from tumorigenesis through additional mechanisms. Collectively, our results demonstrate that MTG16, via its repression of E protein targets, is a key regulator of cell fate decisions during colon homeostasis, colitis, and cancer.Graphical Abstract

Mutated in Colorectal Cancer (MCC) encodes a coiled-coil protein implicated, as its name suggests, in the pathogenesis of hereditary human colon cancer. To date, however, the contributions of MCC to intestinal homeostasis remain unclear. Here, we examine the subcellular localization of MCC, both at the mRNA and protein levels, in the adult intestinal epithelium. Our findings reveal that Mcc transcripts are restricted to proliferating crypt cells, including Lgr5+ stem cells, and that Mcc protein is distinctly associated with the centrosome in these cells. Upon intestinal cellular differentiation, Mcc is redeployed to the non-centrosomal microtubule organizing center (ncMTOC) at the apical domain of villus cells. Using intestinal organoids, we show that the shuttling of the Mcc protein depends on phosphorylation by Casein Kinases 1δ/ε, which are critical modulators of WNT signaling. Together, our findings support a putative role for MCC in establishing and maintaining the cellular architecture of the intestinal epithelium as a component of both the centrosome and ncMTOC.

This paper presents a source-synchronous receiver architecture for use in parallel optical links. The proposed system is reconfigurable, allowing any channel to be used as a clock or data lane. The architecture is designed for mode-division multiplexed (MDM) optical links with forwarded clocks and allows the sensitive clock signal to be placed in the lane with the least amount of optical crosstalk for a given photonic interconnect. This configurability, which accounts for variation in integrated optics by leveraging the more robust electronic chip, optimizes the performance in electronic/optic codesigned solutions and may improve the yield. The architecture contains a dynamic clock distribution network, able to send a reference clock signal from the chosen clock receiver to any other data-configured receiver. The proposed architecture has been implemented on an experimental chip consisting of two receivers designed in the 65-nm CMOS technology. Electrical measurements at 8 Gb/s were done, and bit error rate curves are presented. They demonstrate the ability to swap and repurpose the clock and data inputs between the receivers, with similar sensitivity upon reconfiguration as a proof of concept.

Serine threonine kinase 17A (STK17A) is a ubiquitously expressed kinase originally identified as a regulator of apoptosis; however, whether it functionally contributes to colorectal cancer has not been established. Here, we have analyzed STK17A in colorectal cancer and demonstrated decreased expression of STK17A in primary tumors, which is further reduced in metastatic lesions, indicating a potential role in regulating the metastatic cascade. Interestingly, changes in STK17A expression did not modify proliferation, apoptosis, or sensitivity of colorectal cancer cell lines to treatment with the chemotherapeutic 5-fluorouracil. Instead, STK17A knockdown induced a robust mesenchymal phenotype consistent with the epithelial–mesenchymal transition, including spindle-like cell morphology, decreased expression of adherens junction proteins, and increased migration and invasion. Additionally, overexpression of STK17A decreased cell size and induced widespread membrane blebbing, a phenotype often associated with activation of cell contractility. Indeed, STK17A-overexpressing cells displayed heightened phosphorylation of myosin light chain in a manner dependent on STK17A catalytic activity. Finally, patient-derived tumor organoid cultures were used to more accurately determine STK17A's effect in primary human tumor cells. Loss of STK17A induced morphologic changes, decreased E-cadherin, increased invasion, and augmented organoid attachment on 2D substrates, all together suggesting a more metastatic phenotype. Collectively, these data indicate a novel role for STK17A in the regulation of epithelial phenotypes and indicate its functional contribution to colorectal cancer invasion and metastasis. Implications: Loss of serine threonine kinase 17A occurs in colorectal cancer metastasis, induces mesenchymal morphologies, and contributes to tumor cell invasion and migration in colorectal cancer.

The myeloid translocation gene family member MTG16 is a transcriptional corepressor that relies on the DNA-binding ability of other proteins to determine specificity. One such protein is the ZBTB family member Kaiso, and the MTG16:Kaiso interaction is necessary for repression of Kaiso target genes, such as matrix metalloproteinase-7. Using the azoxymethane and dextran sodium sulfate (AOM/DSS) murine model of colitis-associated carcinoma, we previously determined that MTG16 loss accelerates tumorigenesis and inflammation. However, it was unknown whether this effect was modified by Kaiso-dependent transcriptional repression. To test for a genetic interaction between MTG16 and Kaiso in inflammatory carcinogenesis, we subjected single and double knockout (DKO) mice to the AOM/DSS protocol. Mtg16-/- mice demonstrated increased colitis and tumor burden; in contrast, disease severity in Kaiso-/- mice was equivalent to wild-type controls. Surprisingly, Kaiso deficiency in the context of MTG16 loss reversed injury and pro-tumorigenic responses in the intestinal epithelium following AOM/DSS treatment, and tumor numbers were returned to near to wild-type levels. Transcriptomic analysis of non-tumor colon tissue demonstrated that changes induced by MTG16 loss were widely mitigated by concurrent Kaiso loss, and DKO mice demonstrated downregulation of metabolism and cytokine-associated gene sets with concurrent activation of DNA damage checkpoint pathways as compared with Mtg16-/-. Further, Kaiso knockdown in intestinal enteroids reduced stem- and WNT-associated phenotypes, thus abrogating the induction of these pathways observed in Mtg16-/- samples. Together, these data suggest that Kaiso modifies MTG16-driven inflammation and tumorigenesis and suggests that Kaiso deregulation contributes to MTG16-dependent colitis and CAC phenotypes.

Selenium (Se) is an essential micronutrient of critical importance to mammalian life. Its biological effects are primarily mediated via co-translational incorporation into selenoproteins, as the unique amino acid, selenocysteine. These proteins play fundamental roles in redox signaling and includes the glutathione peroxidases and thioredoxin reductases. Environmental distribution of Se varies considerably worldwide, with concomitant effects on Se status in humans and animals. Dietary Se intake within a narrow range optimizes the activity of Se-dependent antioxidant enzymes, whereas both Se-deficiency and Se-excess can adversely impact health. Se-deficiency affects a significant proportion of the world's population, with hypothyroidism, cardiomyopathy, reduced immunity, and impaired cognition being common symptoms. Although relatively less prevalent, Se-excess can also have detrimental consequences and has been implicated in promoting both metabolic and neurodegenerative disease in humans. Herein, we sought to comprehensively assess the developmental effects of both Se-deficiency and Se-excess on a battery of neurobehavioral and metabolic tests in mice. Se-deficiency elicited deficits in cognition, altered sensorimotor gating, and increased adiposity, while Se-excess was surprisingly beneficial.

Key message Complete lung collapse associated with sarcoidosis is exceedingly rare. Although lymphoma should be ruled out when patients with mediastinal lymphadenopathy develop lung collapse, sarcoidosis should be considered in the differential, especially when associated with fibrosing mediastinitis., Here, we report an extremely rare case of a 47‐year‐old African American female with complete lung collapse associated with sarcoidosis. Although lymphoma should be ruled out when patients with mediastinal lymphadenopathy develop lung collapse, sarcoidosis should be considered in the differential, especially when associated with fibrosing mediastinitis.

Leaking longitudinal joints are commonly observed in adjacent box-beam bridges and are often associated with an assumed loss of load distribution at the leaking joint. To address the lack of test data and general uncertainty in analyzing deteriorated concrete structures, a series of load tests was conducted to determine the load distribution of a deteriorated adjacent concrete box-beam bridge. Load distribution was investigated for the existing structure with leaking joints as well as for the structure following rehabilitation with a noncomposite reinforced concrete deck. The bridge was tested in four conditions: as built, after removal of the bituminous wearing surface, after the shear keys were disabled, and with a reinforced concrete deck installed. Load distribution was assessed for each condition, and the results were compared with design equations. In addition to assessing load distribution of the existing bridge, the results of this study can serve as support for the use of a concrete deck as a rehabilitation strategy to restore load distribution or function as the primary load distribution mechanism of an adjacent box-beam bridge.

This project focused on evaluating the effects of fire-induced damage on concrete bridge elements, including prestressed concrete bridge girders. A series of controlled heating experiments, pool fire tests, material tests, and structural loading tests were conducted. Experimental results indicate that the portion of concrete subjected to temperatures higher than 400°C loses significant amounts of calcium hydroxide (CH). Decomposition of CH increases porosity and causes significant cracking. The portion of concrete exposed to temperatures higher than 400°C should be repaired or replaced. When subjected to ISO-834 standard fire heating, approximately 0.25 in. and 0.75 in. of concrete from the exposed surface are damaged after 40 minutes and 80 minutes of heating, respectively. Prestressed concrete girders exposed to about 50 minutes of hydrocarbon fire undergo superficial concrete material damage with loss of CH and extensive cracking and spalling extending to the depth of 0.75–1.0 in. from the exposed surface. These girders do not undergo significant reduction in flexural strength or shear strength. The reduction in the initial stiffness may be notable due to concrete cracking and spalling. Bridge inspectors can use these findings to infer the extent of material and structural damage to prestressed concrete bridge girders in the event of a fire and develop a post-fire assessment plan.

Monte Carlo simulation (MCS) is one of the most accurate computation methods for dose calculation and image formation in radiation therapy. However, the high computational complexity and long execution time of MCS limits its broad use. In this paper, we present a novel strategy to accelerate MCS using a graphic processing unit (GPU), and we demonstrate the application in mega-voltage (MV) cone-beam computed tomography (CBCT) simulation. A new framework that generates a series of MV projections from a single simulation run is designed specifically for MV-CBCT acquisition. A Geant4-based GPU code for photon simulation is incorporated into the framework for the simulation of photon transport through a phantom volume. The FastEPID method, which accelerates the simulation of MV images, is modified and integrated into the framework. The proposed GPU-based simulation strategy was tested for its accuracy and efficiency in a Catphan 604 phantom and an anthropomorphic pelvis phantom with beam energies at 2.5 MV, 6 MV, and 6 MV FFF. In all cases, the proposed GPU-based simulation demonstrated great simulation accuracy and excellent agreement with measurement and CPU-based simulation in terms of reconstructed image qualities. The MV-CBCT simulation was accelerated by factors of roughly 900–2300 using an NVIDIA Tesla V100 GPU card against a 2.5 GHz AMD Opteron™ Processor 6380.